EP0122036B2 - Powdery pharmaceutical composition for nasal administration - Google Patents

Powdery pharmaceutical composition for nasal administration Download PDF

Info

Publication number
EP0122036B2
EP0122036B2 EP84301546A EP84301546A EP0122036B2 EP 0122036 B2 EP0122036 B2 EP 0122036B2 EP 84301546 A EP84301546 A EP 84301546A EP 84301546 A EP84301546 A EP 84301546A EP 0122036 B2 EP0122036 B2 EP 0122036B2
Authority
EP
European Patent Office
Prior art keywords
water
pharmaceutical composition
absorbing
composition according
derivative
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP84301546A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP0122036A1 (en
EP0122036B1 (en
Inventor
Yoshiki Suzuki
Kunio Sekine
Tsuneji Nagai
Naoki Nambu
Yuji Nishimoto
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Teijin Ltd
Original Assignee
Teijin Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=12492205&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP0122036(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Teijin Ltd filed Critical Teijin Ltd
Publication of EP0122036A1 publication Critical patent/EP0122036A1/en
Application granted granted Critical
Publication of EP0122036B1 publication Critical patent/EP0122036B1/en
Publication of EP0122036B2 publication Critical patent/EP0122036B2/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof

Definitions

  • This invention relates to a powdery pharmaceutical composition adepted for nasal administration. More specifically, this invention relates to a powdery composition adepted for nasal administration which comprises a physiologically active polypeptide or its derivative, such as calcitonin or insulin, and a water-absorbing and water-insoluble base selected from celluloses, starches and cross-linked vinyl polymers and which allows said polypeptide or its derivative to be effectively absorbed through the nasal mucosa when nasally administered.
  • a physiologically active polypeptide or its derivative such as calcitonin or insulin
  • a water-absorbing and water-insoluble base selected from celluloses, starches and cross-linked vinyl polymers and which allows said polypeptide or its derivative to be effectively absorbed through the nasal mucosa when nasally administered.
  • peptide hormones such as insulin and calcitonin have a high molecular weight and that they are readily decomposed by proteolytic enzymes, such as pepsin, trypsin and chymotrypsin, the peptide hormones are not absorbed sufficiently to display a pharmacological effect efficaciously and accordingly they have been administered by parenteral injection.
  • this method may not be regarded as an expedient means, since the preparation is prepared in the form of a liquid, often causing the drug to flow out of the nasal cavity upon its administration into the nose and the use of a surface active agent in its preparation also causes inconvenience.
  • US-A-4,294,829 discloses a pharmaceutical preparation comprising a lower alkyl ether of cellulose and a drug.
  • This pharmaceutical composition is characterized in that its lower alkyl ether of cellulose absorbs moisture on the nasal mucous membrane, and takes the form of a viscous liquid to slowly flow over the nasal mucosa and release the drug slowly. Since a composition of this type takes the form of a viscous liquid in the nasal cavity, a drug with a high molecular weight tends to stay within the lower alkyl ether of cellulose and becomes difficult to release from the composition.
  • DE-A-2 535 258 discloses a pharmaceutical composition for use in a mouth inhaler.
  • the composition comprises soft pellets having a size from 10 to 1000 /1.m which breaks down on inhalation to particles having a size of less than 10 /1.m so that the particles can lodge in the lungs.
  • One of the objects of this invention is to provide a powdery pharmaceutical composition for nasal administration.
  • Another object of this invention is to provide a powdery pharmaceutical composition for nasal administration aimed at application of a physiologically active polypeptide or its derivative.
  • a further object of this invention is to provide a powdery pharmaceutical composition for nasal administration which allows a physiologically active polypeptide or its derivative to be absorbed efficiently through the nasal mucosa without the use of an absorption aid.
  • Still another object of this invention is to provide a powdery pharmaceutical composition for nasal administration which especially allows polypeptides, such as insulin and calcitonin, to be absorbed efficiently through the nasal mucosa without the use of an absorption aid.
  • polypeptides such as insulin and calcitonin
  • a powdery pharmaceutical composition adepted for nasal administration which comprises: (i) a physiologically active polypeptide or its derivative; (ii) a water-absorbing and water-insoluble base selected from celluloses, starches and cross-linked vinyl polymers and (iii) optionally a water-absorbing and water-soluble base, said water-absorbing and water-soluble base being present in an amount of 0.1 to 60 wt%, against the water-absorbing and water-insoluble base; wherein at least 90 wt. % of the particles of said composition have an effective diameter ranging from 10 to 250 /1.m and wherein said particles do not disintegrate on spraying, provided that the composition does not comprise a mixture of bacitracin and starch.
  • the powdery pharmaceutical composition for nasal administration is a composition which allows a polypeptide such as insulin to be absorbed at a satisfactorily high efficiency.
  • the objective drug is a physiologically active polypeptide or its derivative.
  • a polypeptide or its derivative with a molecular weight ranging from 1,000 to 300,000 are desirable in view of the fact that they are easily absorbed through the nasal mucous membrane. Especially those having a molecular weight ranging from 1,000 to 150,000 are more desirable.
  • Desirable physiologically active polypeptides or their derivatives are exemplified in the following.
  • such peptide hormones as insulin, angiotensin, vasopressin, desmopressin, felypressin, protirelin, luteinizing hormone releasing hormone, corticotropin, prolactin, somatropin, thyrotropin, luteinizing hormone, calcitonin, kallikrein, parathryin, glucagon, oxytocin, gastrin, secretin, serum gonadotrophin, growth hormone, erythropoietin, urogastrone and renin; such physiologically active proteins as interferon, interleukin, transferrin, histaglobulin, macrocortine and blood coagulation factor VIII; such enzyme proteins as lysozyme and urokinase; such vaccines as acellular and cellular pertussis vaccine, diphtheria vaccine, tetanus vaccine, and influenza vaccine;
  • peptide hormones are desirable, and peptide hormones are especially more desirable.
  • calcitonin, insulin, luteinizing hormone releasing hormone, desmopressin, vasopressin and oxytocin are particularly desirable and calcitonin and insulin are more particularly desirable.
  • physiologically active proteins interferon is particularly desirable, and among vaccines, influenza vaccine and pertussis vaccine are particularly desirable.
  • the physiologically active polypeptide or its derivative is preferred to be one in the form of a powder.
  • the physiologically active polypeptide or its derivative should desirably be water-soluble in view of the fact it is to be absorbed through the nasal mucous membrane.
  • water-soluble means that the polypeptide or its derivative is soluble on the human nasal mucous membrane or in a similar environment, or more concretely, it is soluble in an aqueous solution at pH around 7.4 at a temperature of about 36 ° C to 37 ° C.
  • polypeptides which are water-insoluble or hardly soluble in water are to be used, it is accordingly advisable, for instance, to adjust their pH, dissolve in water, and freeze-dry, thus making them water-soluble and in the form of powder.
  • polypeptides which are not in the form of powder should desirably be freeze-dried into powder before use.
  • polypeptide or its derivative can be used in combination with human serum albumin, mannitol, sorbitol, aminoacetic acid, amino acid, sodium chloride or phospholipid for the purpose of stabilization, or for the dual purpose of stabilizing and bulking.
  • a base having a duplicity of properties of being water-absorbing and water-insoluble is used.
  • water-absorbing and water-insoluble it is meant that the base has the double properties of being water-absorbing and water-insoluble on the human nasal mucous membrane or in a similar environment, or more concretely, it is water-absorbing and water-insoluble at pH around 7.4 and at a temperature of 36 ° C to 37 ° C or thereabout.
  • the pharmaceutical compositions of this invention are able to absorb the moisture on the nasal mucous membrane upon its administration into the nasal cavity, thus making each particle, which is not in the state of a viscous fluid and does not flow away immediately but diffuses moderately, stay at the site on the nasal mucosa where it adhered and allows the polypeptide or its derivative with a high molecular weight to come into thorough contact with the nasal mucosa, through which they are absorbed at a high efficiency.
  • the selection of such a base as mentioned above for use as the base of a polypeptide or its derivative preparation for nasal application has made it possible to make the polypeptide or its derivative be absorbed effectively and let it display its pharmacological efficacy sufficiently without the use of an absorption aid.
  • the water-absorbing and water-insoluble bases which are to be used in this invention should be distinguished from those lower alkyl ethers of cellulose, or more particularly such lower alkyl ethers of cellulose as hydroxypropyl cellulose which dissolve into a viscous fluid on the nasal mucous membrane.
  • the desirable examples of the water-absorbing and water-insoluble base the following ones may be mentioned.
  • water-absorbing and water-insoluble celluloses such as crystalline cellulose, cellulose, a-cellulose, and cross-linked sodium carboxymethyl cellulose
  • water-absorbing and water-insoluble starches such as hydroxypropyl starch, carboxymethyl starch, cross-linked starch, amylose, amylopectin and pectin
  • cross-linked vinyl polymers such as cross-linked polyvinyl pyrrolidone, cross-linked carboxyvinyl polymer or its salt, cross-linked polyvinyl alcohol and polyhydroxyethylmethacrylate.
  • water-absorbing and water-insoluble celluloses and cross-linked vinyl polymer are desirable, water-absorbing and water-insoluble celluloses are more desirable and crystalline cellulose is especially desirable.
  • cross-linked vinyl polymers cross-linked polyvinylpyrrolidone and cross-linked carboxy vinyl polymer or its salt are desirable.
  • the quantity of a water-absorbing and water-insoluble base to be used varies depending upon the polypeptide or its derivative to be used, it cannot be defined indiscriminately; however, it is desirable in general to use it in appreciable amount of more than 10 times the weight of the polypeptide or its derivative especially more than 15 times, furthermore more than 20 times.
  • said water-absorbing and water-soluble base may be used in combination with a water-absorbing and water-insoluble base.
  • a water-absorbing and water-soluble base adds some degree of solubility to a water-absorbing and water-insoluble base to produce the following effect.
  • the particles which comprise a water-absorbing and water-insoluble base and a polypeptide or its derivative are dispersed over the nasal mucous membrane, and the water-absorbing and water-soluble base is dissolved into the state of a viscous fluid, which gives some degree of viscosity and flowage to the whole base of this invention, thus allowing the polypeptide or its derivative to be absorbed slowly, which is known as a sustained release effect.
  • the water-absorbing and water-soluble base may be used by simply mixing it with the water-absorbing and water-insoluble base or by mixing it with the polypeptide or its derivative at the time of their freeze-drying.
  • the mixture assumes a state in which particles of the polypeptide or its derivative are dispersed among particles of the water-absorbing and water-soluble base and the final product of pharmaceutical composition comes to have much more sustained relese effect.
  • water-absorbing and water-soluble base to be used in this invention there are, for instance, polyacrylates such as sodium polyacrylate, potassium polyacrylate and ammonium polyacrylate; lower alkyl ethers of cellulose such as methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and sodium carboxymethyl cellulose; polvyinyl pyrrolidone; amylose; polyethyleneglycol; and pullulan.
  • polyacrylates such as sodium polyacrylate; lower alkyl ethers of cellulose such as methyl cellulose, hydroxypropyl cellulose and sodium carboxymethyl cellulose; polyethyleneglycol; and polyvinyl pyrrolidone are especially desirable.
  • the quantity of water-absorbing and water-soluble base to be used should be 0.1 to 60 wt%, or desirably 1 to 50 wt%, against the water-absorbing and water-insoluble base.
  • At least 90 wt% particles of the powdery composition have an effective diameter of 10 to 250 /1.m.
  • the powdery composition of this invention may have any of the structures such as one in which the water-absorbing and water-insoluble base and polypeptide or its derivative form independent particles, one in which the polypeptide or its derivative particles are adhered to the surface of the water-absorbing and water-insoluble base particle, one in which the polypeptide or its derivative particles are dispersed in the water-absorbing and water-insoluble base particle, both forming separate phases of their own, or one in which the polypeptide or its derivative particles are closely dispersed in the water-absorbing and water-insoluble base particle, thus forming uniform dispersion.
  • the powdery composition of this invention which has a structure in which the water-absorbing and water-insoluble base and polypeptide or its derivative form independent particles or the polypeptide or its derivative particles are adhered to the surface of the water-absorbing and water-insoluble base particles, can be prepared by first adding polypeptide or its derivative to a water-absorbing and water-insoluble base, then mixing them by a mechanical process, and finally filtering them to obtain the desired composition with more than 90 wt% of its particles measuring 10 to 250 /1.m in effective diameter.
  • both bases may be mixed together simultaneously with the polypeptide or its derivatives in the mechanical mixing process.
  • the powdery composition of this invention which has a structure in which the polypeptide or its derivative particles are dispersed in the water-absorbing and water-insoluble base particles, both forming separate phases of their own, or the polypeptide or its derivative particles are closely dispersed in the water-absorbing and water-insoluble base particles, thus forming a uniform dispersion, can be obtained by following the procedure mentioned below. It is prepared by firstly mixing the polypeptide or its derivative with a water-absorbing and water-insoluble base by mechanical means, then compacting the obtained mixture under pressure, further pulverizing the compacted mixture, and finally filtering the resulting pulverulence to obtain the desired composition with more than 90 wt% its particles measuring 10 to 250 /1.m in effective diameter.
  • the powdery composition can also be obtained by thoroughly mixing the polypeptide or its derivative with a water-absorbing and water-insoluble base in water to make a thin smooth pasty mixture, drying and pulverizing the mixture according to ordinary methods, and finally passing the pulverized composition through a sieve.
  • a water-absorbing and water-soluble base in the case where a water-absorbing and water-soluble base is to be used jointly, it may be admixed with the polypeptide or its derivative and a water-absorbing and water-insoluble base in the mechanical mixing process, followed by the abovementioned processes of compacting, etc., or a water-absorbing and water-soluble base may be introduced into the process wherein the polypeptide or its derivative is mixed with a water-absorbing and water-insoluble base in the presence of water.
  • the powdery pharmaceutical composition of this invention may, if desired, contain any of the known additives such as coloring agents, preservatives, antiseptics, corrigents, etc.
  • coloring agents there are, for instance, ,8-carotene, Red No. 2 and Blue No. 1
  • preservatives there are for instance stearic acid, ascorbyl stearate and ascorbic acid
  • antiseptics there are for instance p-hydroxybenzoate, phenol and chlorobutanol
  • corrigents there are for instance menthol and citrus perfume.
  • the powdery pharmaceutical composition of this invention can be directly used as a powder for a unit dosage form.
  • the powder can be filled in capsules such as hard gelatin capsules.
  • the method of pernasally applying the powdery preparation to the nasal cavity by spraying there is, for instance, a method in which a capsule filled with the powdery preparation is placed in a sprayer, which is exclusively designed for this purpose and equipped with a needle, then the capsule is pierced with the needle to have minute holes on both the top and bottom, and thereafter jets of powder are sent into the nasal cavity by means of ballooning, etc.
  • FIG. 1 shows the decrease (%) of the plasma glucose levels from that before administration of insulin.
  • the values shown in Fig. 1 are the average values of four Beagle dogs.
  • the change in plasma glucose levels after the nasal administration of 5 units/10 ul/kg, by use of a micropipette, of an aqueous suspension of original insulin powder is shown by a broken line in Fig. 1 for the sake of comparison.
  • Fig. 1 shows the decrease in plasma glucose levels from that before administration of insulin.
  • Example 1 (1) indicates the case where crystalline cellulose was used as the base (Example 1, (a)), (2) the case where freeze-dried insulin-sodium polyacrylate and crystalline cellulose were used (Example 1, (b)), (3) the case were lactose was used as the base (Example 1, (d)), and (4) the case where hydroxypropyl cellulose was used as the base (Example 1, (e)) respectively.
  • compositions in which crystalline cellulose is used show a highly efficient absorption of insulin and that the composition in which sodium polyacrylate is used in combination with crystalline cellulose show a highly efficient absorption of insulin as well as a sustained release effect.
  • (1) indicates the case where crystalline cellulose was used as the base (Example 3, (a)), (2) the case where lactose was used as the base (Example 3, (b)), and (3) the case where hydroxypropyl cellulose was used as the base (Example 3, (c)) respectively.
  • composition of this invention shows a highly efficient absorption of insulin.
  • 2,000 mg of crystalline cellulose and 0.5 mg of freeze-dried [ASU 1.7 ]-eel calcitonin (4,000 MRC units/mg) were placed in a mortar and mixed most thoroughly to obtain a uniform powdery composition.
  • the obtained powdery composition contained about 1 MRC unit/mg of [ASU1.7]-eel calcitonin.
  • the powdery composition was filled in the prescribed capsules with the capsule filler, each capsule containing 10 to 50 mg, to obtain a preparation for human nasal application.
  • the powdery composition thus obtained was then encapsulated according to the prescription to give a preparation for human nasal application.
  • crystalline cellulose 950 mg was placed in a mortar, to which 50 mg of interferon (10 5 units/mg), which had been freeze-dried together with human serum albumin, was added. They were mixed thoroughly to obtain a uniform powdery composition.
  • the powdery composition thus obtained contained 5,000 units/mg of interferon and was encapsulated according to the prescription to obtain a preparation for human nasal application.
  • 2,000 mg of crystalline cellulose and 0.5 mg (4,000 MRC units/mg) of freeze-dried [ASU1.7]-eel calcitonin or 1.0 mg (2,000 MRC units/mg) of salmon calcitonin were placed in a mortar and mixed well to obtain a uniform powdery composition.
  • the obtained powdery composition contained about 1 MRC unit/mg of [ASU1.7]-eel calcitonin or salmon calcitonin.
  • 100 mg of the powdery composition and 900 mg of crystalline cellulose were placed in a mortar and mixed thoroughly to obtain a uniform powdery composition, at least 90 wt% of the particles of which had a particle diameter of 10 to 250 ⁇ m.
  • powdery composition contained 1 MRC unit/mg of the salmon calcitonin. 10 to 50 mg of the powdery composition thus obtained was then encapsulated according to the prescription to give a preparation for human nasal application.
  • 200 mg of of the powdery composition and 800 mg of crystalline cellulose were placed in a mortar and mixed thoroughly to obtain a powdery composition, at least 90 wt% of the particles of which had a particle diameter of 10 to 250 ⁇ m.
  • powdery composition contained 1.6 MRC units/mg of [ASU 1.7 ]-eel calciton. 10 to 50 mg of the powdery composition thus obtained was then encapsulated according to the prescription to give a preparation for human nasal application.
  • PT formalin-detoxificated Partussis toxin
  • F-HA formalin-treated filamentous hemagglutinin
  • the obtained powdery composition contained about totally 2 ⁇ g/mg of both components.
  • powdery freeze-dried influenza HA vaccine 800 mg of hydroxypropylcellulose and 200 mg of powdery freeze-dried influenza HA vaccine were placed in a mortar and mixed well to obtain a uniform powdery composition.
  • the powdery composition contained about 200 ⁇ /mg of freeze-dried influenza HA vaccine.
  • 50 mg of the powdery composition and 950 mg of crystalline cellulose were placed in a mortar and mixed well to give a uniform powdery composition, at least 90 wt% of the particles of which had a particle diameter of 10 to 150 ⁇ m.
  • powdery composition contained 10 ⁇ m/mg of freeze-dried influenza HA vaccine.
  • 10 to 30 mg of powdery composition thus obtained was then encapsulated according to the prescription to give a preparation for human nasal application.
EP84301546A 1983-03-09 1984-03-08 Powdery pharmaceutical composition for nasal administration Expired - Lifetime EP0122036B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP58037244A JPS59163313A (ja) 1983-03-09 1983-03-09 経鼻投与用ペプチドホルモン類組成物
JP37244/83 1983-03-09

Publications (3)

Publication Number Publication Date
EP0122036A1 EP0122036A1 (en) 1984-10-17
EP0122036B1 EP0122036B1 (en) 1989-02-08
EP0122036B2 true EP0122036B2 (en) 1994-11-02

Family

ID=12492205

Family Applications (1)

Application Number Title Priority Date Filing Date
EP84301546A Expired - Lifetime EP0122036B2 (en) 1983-03-09 1984-03-08 Powdery pharmaceutical composition for nasal administration

Country Status (4)

Country Link
US (1) US4613500A (ko)
EP (1) EP0122036B2 (ko)
JP (1) JPS59163313A (ko)
DE (1) DE3476633D1 (ko)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003004048A1 (en) * 2001-07-05 2003-01-16 Translational Research Ltd. Compositions for nasal administration of insulin
US6737045B2 (en) 1994-03-07 2004-05-18 Nektar Therapeutics Methods and compositions for the pulmonary delivery insulin
US6797258B2 (en) 1992-07-08 2004-09-28 Nektar Therapeutics Compositions and methods for the pulmonary delivery of aerosolized macromolecules
US7713929B2 (en) 2006-04-12 2010-05-11 Biodel Inc. Rapid acting and long acting insulin combination formulations
US7744925B2 (en) 1994-12-02 2010-06-29 Quadrant Drug Delivery Limited Solid dose delivery vehicle and methods of making same
US8084420B2 (en) 2005-09-29 2011-12-27 Biodel Inc. Rapid acting and long acting insulin combination formulations
US8337895B2 (en) 2000-06-30 2012-12-25 Novartis Ag Spray drying process control of drying kinetics
US8802149B2 (en) 1996-12-31 2014-08-12 Novartis Pharma Ag Systems and processes for spray drying hydrophobic and hydrophilic components
US9060927B2 (en) 2009-03-03 2015-06-23 Biodel Inc. Insulin formulations for rapid uptake

Families Citing this family (222)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8514090D0 (en) * 1985-06-04 1985-07-10 Sandoz Ltd Organic compounds
JPS61267528A (ja) * 1984-11-26 1986-11-27 Yamanouchi Pharmaceut Co Ltd 吸収促進剤を含有するカルシトニン経鼻剤
JPS61137828A (ja) * 1984-12-07 1986-06-25 Shionogi & Co Ltd γ−インタ−フエロン製剤組成物
JPS61194034A (ja) * 1985-02-25 1986-08-28 Teijin Ltd 経鼻投与用粉末状組成物
US5503841A (en) * 1985-09-20 1996-04-02 Cetus Oncology Corporation Human IL-2 as a vaccine adjuvant
US5643565A (en) * 1985-09-20 1997-07-01 Chiron Corporation Human IL-2 as a vaccine adjuvant
DE3601923A1 (de) * 1986-01-23 1987-07-30 Behringwerke Ag Nasal applizierbares arzneimittel, verfahren zu seiner herstellung und seine verwendung
US4734401A (en) * 1986-03-17 1988-03-29 W. R. Grace & Co. Process for spray drying amino acid compositions
DK179286D0 (da) * 1986-04-18 1986-04-18 Nordisk Gentofte Insulinpraeparat
CA1291036C (en) * 1986-04-23 1991-10-22 Edwin I. Stoltz Nasal administration of drugs
CA1257199A (en) * 1986-05-20 1989-07-11 Paul Y. Wang Preparation containing bioactive macromolecular substance for multi-months release in vivo
US4962091A (en) * 1986-05-23 1990-10-09 Syntex (U.S.A.) Inc. Controlled release of macromolecular polypeptides
NL8701143A (nl) * 1986-05-27 1987-12-16 Sandoz Ag Farmaceutische preparaten.
IT1204400B (it) * 1986-06-20 1989-03-01 Sclavo Spa Composizioni farmaceutiche contenente una calcitonina
NL8720442A (nl) * 1986-08-18 1989-04-03 Clinical Technologies Ass Afgeefsystemen voor farmacologische agentia.
USRE35862E (en) * 1986-08-18 1998-07-28 Emisphere Technologies, Inc. Delivery systems for pharmacological agents encapsulated with proteinoids
DE3726517A1 (de) * 1986-08-18 1988-03-03 Sandoz Ag Nasale zusammensetzungen, welche octreotid enthalten
EP0257956B2 (en) 1986-08-19 2000-11-22 Genentech, Inc. Use of polypeptide growth factors and cytokines for the manufacture of a device and of a dispersion
US5075109A (en) * 1986-10-24 1991-12-24 Southern Research Institute Method of potentiating an immune response
US5811128A (en) * 1986-10-24 1998-09-22 Southern Research Institute Method for oral or rectal delivery of microencapsulated vaccines and compositions therefor
JPH0688898B2 (ja) * 1986-10-31 1994-11-09 帝人株式会社 アスコルビン酸類を含有する経鼻投与用粉末状組成物
JP2505430B2 (ja) * 1986-11-04 1996-06-12 帝人株式会社 塩基性アミノ酸を含有する経鼻投与用粉末状組成物
WO1988005661A1 (en) * 1987-01-30 1988-08-11 Biomed Research Consultants, Limited Vasopressin-based pharmaceutical compositions
GB8712176D0 (en) * 1987-05-22 1987-06-24 Cosmas Damian Ltd Drug delivery system
US5690954A (en) * 1987-05-22 1997-11-25 Danbiosyst Uk Limited Enhanced uptake drug delivery system having microspheres containing an active drug and a bioavailability improving material
IT1222395B (it) * 1987-07-30 1990-09-05 Pierrel Spa Composizione farmaceutica per somministrazione intranasale comprendente l'ormone ghrh,un agonista colinergico e/o un sale biliare
US5059587A (en) * 1987-08-03 1991-10-22 Toyo Jozo Company, Ltd. Physiologically active peptide composition for nasal administration
DE3726324A1 (de) * 1987-08-07 1989-02-16 Hoechst Ag Cyclopeptide als resorptionsfoerderer bei applikation auf die schleimhaeute
PT88490B (pt) * 1987-09-14 1992-11-30 Novo Nordisk As Processo para a preparacao de composicoes farmaceuticas para libertacao nao-enterica trans-mucosa contendo monossacaridos ou oligossacaridos
IT1222734B (it) * 1987-09-25 1990-09-12 Scalvo S P A Formulaziopne farmaceutiche e forme di dosaggio per la somminaistarzione rettale di calcitonina
GB8723846D0 (en) * 1987-10-10 1987-11-11 Danbiosyst Ltd Bioadhesive microsphere drug delivery system
CA1336401C (en) * 1987-10-15 1995-07-25 Brian H. Vickery Intranasal administration of polypeptides in powdered form
ES2061688T3 (es) * 1987-11-13 1994-12-16 Smithkline Beecham Farma Composiciones farmaceuticas que comprenden una calcitonina y un glicirricinato como mejorador de la absorcion.
FR2634376B1 (fr) * 1988-07-21 1992-04-17 Farmalyoc Nouvelle forme unitaire, solide et poreuse comprenant des microparticules et/ou des nanoparticules, ainsi que sa preparation
JPH02104531A (ja) * 1988-10-14 1990-04-17 Toyo Jozo Co Ltd 経鼻投与用生理活性ペプチド組成物
KR900701310A (ko) * 1988-11-14 1990-12-01 오스카 아끼히꼬 인터페론 경비투여용 제제
US5567682A (en) * 1988-12-16 1996-10-22 Advanced Peptides And Biotechnology Sciences Method of treating Alzheimer's disease
JP2704546B2 (ja) * 1989-04-04 1998-01-26 光利 太良 Ａｔｌｌ治療用吸入剤
IT8920486A0 (it) * 1989-05-12 1989-05-12 Isf Spa Composizioni farmaceutiche.
US5707644A (en) * 1989-11-04 1998-01-13 Danbiosyst Uk Limited Small particle compositions for intranasal drug delivery
GB2237510B (en) * 1989-11-04 1993-09-15 Danbiosyst Uk Small particle drug compositions for nasal administration
US5624898A (en) 1989-12-05 1997-04-29 Ramsey Foundation Method for administering neurologic agents to the brain
US5175146A (en) * 1989-12-05 1992-12-29 Vical, Inc. Synthetic calcitonin peptides
US6407061B1 (en) 1989-12-05 2002-06-18 Chiron Corporation Method for administering insulin-like growth factor to the brain
US5364840A (en) * 1989-12-05 1994-11-15 Vical, Inc. Synthetic calcitonin peptides
US5188825A (en) * 1989-12-28 1993-02-23 Iles Martin C Freeze-dried dosage forms and methods for preparing the same
GB9001635D0 (en) * 1990-01-24 1990-03-21 Ganderton David Aerosol carriers
US5376386A (en) * 1990-01-24 1994-12-27 British Technology Group Limited Aerosol carriers
JPH05963A (ja) * 1990-04-13 1993-01-08 Toray Ind Inc ポリペプチド類組成物
AU7880991A (en) * 1990-05-10 1991-11-27 Novo Nordisk A/S A pharmaceutical preparation containing n-glycofurols and n-ethylene glycols
DE59007645D1 (de) * 1990-06-21 1994-12-08 Edith Dr Huland Verwendung zytokinhaltiger Aerosole und zytokinhaltige Aerosole selbst.
US5780012A (en) * 1990-06-21 1998-07-14 Huland; Edith Method for reducing lung afflictions by inhalation of cytokine solutions
US6099856A (en) * 1992-06-15 2000-08-08 Emisphere Technologies, Inc. Active agent transport systems
US5447728A (en) * 1992-06-15 1995-09-05 Emisphere Technologies, Inc. Desferrioxamine oral delivery system
US5541155A (en) * 1994-04-22 1996-07-30 Emisphere Technologies, Inc. Acids and acid salts and their use in delivery systems
US5443841A (en) * 1992-06-15 1995-08-22 Emisphere Technologies, Inc. Proteinoid microspheres and methods for preparation and use thereof
US5629020A (en) 1994-04-22 1997-05-13 Emisphere Technologies, Inc. Modified amino acids for drug delivery
US5714167A (en) 1992-06-15 1998-02-03 Emisphere Technologies, Inc. Active agent transport systems
US5693338A (en) * 1994-09-29 1997-12-02 Emisphere Technologies, Inc. Diketopiperazine-based delivery systems
US6331318B1 (en) * 1994-09-30 2001-12-18 Emisphere Technologies Inc. Carbon-substituted diketopiperazine delivery systems
US5578323A (en) 1992-06-15 1996-11-26 Emisphere Technologies, Inc. Proteinoid carriers and methods for preparation and use thereof
US6221367B1 (en) 1992-06-15 2001-04-24 Emisphere Technologies, Inc. Active agent transport systems
IL99699A (en) * 1990-10-10 2002-04-21 Autoimmune Inc Drug with the option of oral, intra-intestinal, or inhaled dosing for suppression of autoimmune response associated with type I diabetes
GB9101592D0 (en) * 1991-01-24 1991-03-06 Glaxo Group Ltd Compositions
DK49791D0 (da) * 1991-03-20 1991-03-20 Novo Nordisk As Nasalt pulverpraeparat
IT1247472B (it) * 1991-05-31 1994-12-17 Fidia Spa Processo per la preparazione di microsfere contenenti componenti biologicamente attivi.
DE4222647A1 (de) * 1991-07-15 1993-01-21 Sandoz Ag Peptid-zubereitungen
WO1993001826A1 (en) * 1991-07-19 1993-02-04 East Carolina University Method of treating asthma
RU2054180C1 (ru) * 1991-08-21 1996-02-10 Жирнов Олег Петрович (н/п) Способ лечения вирусных респираторных инфекций
US5792451A (en) * 1994-03-02 1998-08-11 Emisphere Technologies, Inc. Oral drug delivery compositions and methods
US5811127A (en) * 1992-06-15 1998-09-22 Emisphere Technologies, Inc. Desferrioxamine oral delivery system
ATE220327T1 (de) 1992-09-29 2002-07-15 Inhale Therapeutic Syst Pulmonale abgabe von aktiven fragmenten des parathormons
US5401516A (en) * 1992-12-21 1995-03-28 Emisphere Technologies, Inc. Modified hydrolyzed vegetable protein microspheres and methods for preparation and use thereof
US5354934A (en) † 1993-02-04 1994-10-11 Amgen Inc. Pulmonary administration of erythropoietin
US6090925A (en) * 1993-03-09 2000-07-18 Epic Therapeutics, Inc. Macromolecular microparticles and methods of production and use
US5981719A (en) * 1993-03-09 1999-11-09 Epic Therapeutics, Inc. Macromolecular microparticles and methods of production and use
WO1994020070A1 (en) * 1993-03-11 1994-09-15 Secretech, Inc. Polymeric mucoadhesives in the delivery of immunogens at mucosal surfaces
US5709861A (en) * 1993-04-22 1998-01-20 Emisphere Technologies, Inc. Compositions for the delivery of antigens
AU6819294A (en) * 1993-04-22 1994-11-08 Emisphere Technologies, Inc. Oral drug delivery compositions and methods
US5643957A (en) * 1993-04-22 1997-07-01 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
US5958457A (en) * 1993-04-22 1999-09-28 Emisphere Technologies, Inc. Compositions for the delivery of antigens
TW402506B (en) * 1993-06-24 2000-08-21 Astra Ab Therapeutic preparation for inhalation
US20010003739A1 (en) * 1993-06-24 2001-06-14 Astrazeneca Ab Systemic administration of a therapeutic preparation
US6632456B1 (en) 1993-06-24 2003-10-14 Astrazeneca Ab Compositions for inhalation
US6794357B1 (en) 1993-06-24 2004-09-21 Astrazeneca Ab Compositions for inhalation
IS1796B (is) * 1993-06-24 2001-12-31 Ab Astra Fjölpeptíð lyfjablanda til innöndunar sem einnig inniheldur eykjaefnasamband
US5830853A (en) * 1994-06-23 1998-11-03 Astra Aktiebolag Systemic administration of a therapeutic preparation
US5747445A (en) * 1993-06-24 1998-05-05 Astra Aktiebolag Therapeutic preparation for inhalation
SE9303574D0 (sv) * 1993-11-01 1993-11-01 Kabi Pharmacia Ab Composition for drug delivery and method the manufacturing thereof
US6051256A (en) 1994-03-07 2000-04-18 Inhale Therapeutic Systems Dispersible macromolecule compositions and methods for their preparation and use
AU696387B2 (en) * 1994-05-18 1998-09-10 Inhale Therapeutic Systems, Inc. Methods and compositions for the dry powder formulation of interferons
US6165976A (en) * 1994-06-23 2000-12-26 Astra Aktiebolag Therapeutic preparation for inhalation
US6586006B2 (en) 1994-08-04 2003-07-01 Elan Drug Delivery Limited Solid delivery systems for controlled release of molecules incorporated therein and methods of making same
SE9404468D0 (sv) * 1994-12-22 1994-12-22 Astra Ab Powder formulations
NZ298169A (en) 1994-12-22 1999-09-29 Astra Ab Aerosol drug formulation; comprises hydrofluoroalkane propellant, medicament for inhalation and a surfactant
US6524557B1 (en) 1994-12-22 2003-02-25 Astrazeneca Ab Aerosol formulations of peptides and proteins
DK0806945T3 (da) * 1994-12-22 2003-08-04 Astrazeneca Ab Terapeutisk præparat til inhalering, indeholdende parathyroideahormon, PTH
EP0726075A1 (en) * 1995-02-08 1996-08-14 Therapicon Srl Pharmaceutical non-inorganic saline solutions for endonasal administration
US5989539A (en) * 1995-03-31 1999-11-23 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
US5965121A (en) * 1995-03-31 1999-10-12 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
CN1151836C (zh) * 1995-03-31 2004-06-02 艾米斯菲尔技术有限公司 用作传送活性剂的化合物和组合物
US6001347A (en) 1995-03-31 1999-12-14 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
US5650386A (en) * 1995-03-31 1997-07-22 Emisphere Technologies, Inc. Compositions for oral delivery of active agents
US6090958A (en) * 1995-03-31 2000-07-18 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
US5866536A (en) * 1995-03-31 1999-02-02 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
US5820881A (en) * 1995-04-28 1998-10-13 Emisphere Technologies, Inc. Microspheres of diamide-dicarboxylic acids
US6428771B1 (en) 1995-05-15 2002-08-06 Pharmaceutical Discovery Corporation Method for drug delivery to the pulmonary system
US5824345A (en) * 1995-06-07 1998-10-20 Emisphere Technologies, Inc. Fragrances and flavorants
US5667806A (en) * 1995-06-07 1997-09-16 Emisphere Technologies, Inc. Spray drying method and apparatus
US5750147A (en) 1995-06-07 1998-05-12 Emisphere Technologies, Inc. Method of solubilizing and encapsulating itraconazole
US6051258A (en) * 1995-06-07 2000-04-18 Emisphere Technologies, Inc. Proteinoid emulsions and methods for preparation and use thereof
JP3098401B2 (ja) * 1995-07-12 2000-10-16 株式会社エルティーティー研究所 経鼻投与用製剤
WO1997010197A1 (en) * 1995-09-11 1997-03-20 Emisphere Technologies, Inc. METHOD FOR PREPARING φ-AMINOALKANOIC ACID DERIVATIVES FROM CYCLOALKANONES
JP3263598B2 (ja) * 1995-11-01 2002-03-04 有限会社ドット 経鼻吸収用生理活性ペプチド組成物
US6270795B1 (en) 1995-11-09 2001-08-07 Microbiological Research Authority Method of making microencapsulated DNA for vaccination and gene therapy
KR100568436B1 (ko) * 1996-02-27 2007-04-25 데이진 가부시키가이샤 분말상경비투여조성물
SI9720025A (sl) 1996-03-29 1999-08-31 Emishphere Technologies, Inc. Spojine in sestavki za prenos aktivne snovi
EP0904065A4 (en) 1996-06-14 2000-06-14 Emisphere Tech Inc MICRO-ENCLOSED FRAGRANCES AND PRODUCTION METHOD
JP3020141B2 (ja) * 1996-10-07 2000-03-15 株式会社富士薬品 経鼻投与用製剤
US20070185032A1 (en) * 1996-12-11 2007-08-09 Praecis Pharmaceuticals, Inc. Pharmaceutical formulations for sustained drug delivery
US5968895A (en) 1996-12-11 1999-10-19 Praecis Pharmaceuticals, Inc. Pharmaceutical formulations for sustained drug delivery
US5879681A (en) * 1997-02-07 1999-03-09 Emisphere Technolgies Inc. Compounds and compositions for delivering active agents
US5939381A (en) * 1997-02-07 1999-08-17 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
US6313088B1 (en) 1997-02-07 2001-11-06 Emisphere Technologies, Inc. 8-[(2-hydroxy-4-methoxy benzoyl) amino]-octanoic acid compositions for delivering active agents
US5876710A (en) * 1997-02-07 1999-03-02 Emisphere Technologies Inc. Compounds and compositions for delivering active agents
US6060513A (en) * 1997-02-07 2000-05-09 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
US5990166A (en) * 1997-02-07 1999-11-23 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
US5804688A (en) * 1997-02-07 1998-09-08 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
US6358504B1 (en) 1997-02-07 2002-03-19 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
GB9707934D0 (en) * 1997-04-18 1997-06-04 Danbiosyst Uk Improved delivery of drugs to mucosal surfaces
US5863944A (en) * 1997-04-30 1999-01-26 Emisphere Technologies, Inc. Compounds and compositions for delivering active agents
US5962710A (en) * 1997-05-09 1999-10-05 Emisphere Technologies, Inc. Method of preparing salicyloylamino acids
US8765177B2 (en) * 1997-09-12 2014-07-01 Columbia Laboratories, Inc. Bioadhesive progressive hydration tablets
US7153845B2 (en) * 1998-08-25 2006-12-26 Columbia Laboratories, Inc. Bioadhesive progressive hydration tablets
US6309623B1 (en) 1997-09-29 2001-10-30 Inhale Therapeutic Systems, Inc. Stabilized preparations for use in metered dose inhalers
US6565885B1 (en) 1997-09-29 2003-05-20 Inhale Therapeutic Systems, Inc. Methods of spray drying pharmaceutical compositions
US20060165606A1 (en) 1997-09-29 2006-07-27 Nektar Therapeutics Pulmonary delivery particles comprising water insoluble or crystalline active agents
TWI243687B (en) 1998-04-21 2005-11-21 Teijin Ltd Pharmaceutical composition for application to mucosa
US6190699B1 (en) * 1998-05-08 2001-02-20 Nzl Corporation Method of incorporating proteins or peptides into a matrix and administration thereof through mucosa
US7022683B1 (en) 1998-05-13 2006-04-04 Carrington Laboratories, Inc. Pharmacological compositions comprising pectins having high molecular weights and low degrees of methoxylation
DE19826628C1 (de) * 1998-06-17 2000-07-20 Werner Kern Intranasale Verwendung von Insulin bei Hirnleistungsstörungen
RS49890B (sr) * 1998-07-08 2008-08-07 Kirin-Amgen Inc., Preparat u formi praška koji sadrži medicinsko sredstvo velike molekulske težine za primenu preko sluzokože
AU762145C (en) * 1998-08-26 2005-03-17 Teijin Limited Powdery pernasal compositions
US7273618B2 (en) * 1998-12-09 2007-09-25 Chiron Corporation Method for administering agents to the central nervous system
RU2140285C1 (ru) * 1999-01-25 1999-10-27 Гапонюк Петр Яковлевич Противовирусное средство - капли в нос "гриппферон"
US6258857B1 (en) * 1999-02-04 2001-07-10 Kyowa Industrial Co., Ltd. Internal liquid composition contained as internal liquid in a releasing container and releasing container product
US9006175B2 (en) 1999-06-29 2015-04-14 Mannkind Corporation Potentiation of glucose elimination
EP1196430B1 (en) 1999-06-29 2012-02-15 MannKind Corporation Purification and stabilization of peptide and protein pharmaceutical agents
US7678087B2 (en) * 1999-09-29 2010-03-16 Heska Corporation Equine intranasal delivery system
US6398774B1 (en) 1999-09-29 2002-06-04 Heska Corporation Intranasal delivery system
AR026073A1 (es) 1999-10-20 2002-12-26 Nycomed Gmbh Composicion farmaceutica acuosa que contiene ciclesonida
JP2003535042A (ja) * 2000-01-20 2003-11-25 バジリア ファルマスーチカ アーゲー 鼻腔に投与可能な環式ペプチド組成物
US20030138460A1 (en) * 2000-02-08 2003-07-24 Allergan, Inc Methods of treating animals with botulinum toxin pharmaceutical compositions
US20060269575A1 (en) * 2000-02-08 2006-11-30 Allergan, Inc. Botulinum toxin pharmaceutical compositions formulated with recombinant albumin
US8632785B2 (en) * 2000-02-08 2014-01-21 Allergan, Inc. Clostridial toxin pharmaceutical composition containing a gelatin fragment
US7780967B2 (en) * 2000-02-08 2010-08-24 Allergan, Inc. Reduced toxicity Clostridial toxin pharmaceutical compositions
US20030118598A1 (en) * 2000-02-08 2003-06-26 Allergan, Inc. Clostridial toxin pharmaceutical compositions
NZ520201A (en) * 2000-02-08 2004-04-30 Allergan Inc Botulinum toxin pharmaceutical compositions comprising a polysaccharide
MXPA02001323A (es) 2000-05-10 2004-07-16 Alliance Pharma Microgranulos con base fosfolipida para la liberacion de farmaco.
US7871598B1 (en) 2000-05-10 2011-01-18 Novartis Ag Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use
US8404217B2 (en) 2000-05-10 2013-03-26 Novartis Ag Formulation for pulmonary administration of antifungal agents, and associated methods of manufacture and use
GB0011807D0 (en) * 2000-05-16 2000-07-05 Quadrant Holdings Cambridge Formulation for inhalation
DE60142487D1 (de) * 2000-10-13 2010-08-12 Nat Inst Of Advanced Ind Scien Verfahren zur herstellung von liposomen
GB0027357D0 (en) 2000-11-09 2000-12-27 Bradford Particle Design Plc Particle formation methods and their products
US6777000B2 (en) 2001-02-28 2004-08-17 Carrington Laboratories, Inc. In-situ gel formation of pectin
US7494669B2 (en) 2001-02-28 2009-02-24 Carrington Laboratories, Inc. Delivery of physiological agents with in-situ gels comprising anionic polysaccharides
US7244703B2 (en) * 2001-06-22 2007-07-17 Bentley Pharmaceuticals, Inc. Pharmaceutical compositions and methods for peptide treatment
AU2002366267B2 (en) * 2001-11-19 2007-05-10 Becton, Dickinson And Company Pharmaceutical compositions in particulate form
ATE508735T1 (de) 2001-12-19 2011-05-15 Novartis Ag Pulmonale verabreichung von aminoglykosiden
US7666876B2 (en) * 2002-03-19 2010-02-23 Vernalis (R&D) Limited Buprenorphine formulations for intranasal delivery
ES2425392T3 (es) 2002-03-20 2013-10-15 Mannkind Corporation Cartucho para un aparato de inhalación
GB0216562D0 (en) 2002-04-25 2002-08-28 Bradford Particle Design Ltd Particulate materials
US9339459B2 (en) 2003-04-24 2016-05-17 Nektar Therapeutics Particulate materials
WO2003097080A1 (en) * 2002-05-15 2003-11-27 Sun Pharmaceutical Industries Limited A stable aqueous composition of a peptide
US20090035260A1 (en) * 2002-07-29 2009-02-05 Therapicon Srl Enhanced nasal composition of active peptide
GB0300531D0 (en) 2003-01-10 2003-02-12 West Pharm Serv Drug Res Ltd Pharmaceutical compositions
WO2004073729A1 (ja) 2003-02-21 2004-09-02 Translational Research Ltd. 薬物の経鼻投与用組成物
KR100974482B1 (ko) 2003-03-27 2010-08-10 가부시키가이샤 바이오악티스 비강용 분말 약제 투약 장치
US20060193825A1 (en) * 2003-04-29 2006-08-31 Praecis Phamaceuticals, Inc. Pharmaceutical formulations for sustained drug delivery
US20050112087A1 (en) * 2003-04-29 2005-05-26 Musso Gary F. Pharmaceutical formulations for sustained drug delivery
ATE474591T1 (de) 2003-12-08 2010-08-15 Cpex Pharmaceuticals Inc Pharmazeutische zusammensetzungen und verfahren für die insulinbehandlung
ITMI20040235A1 (it) * 2004-02-13 2004-05-13 Therapicon Srl Preparazione farmaceutica per il cavo orale
US20080090753A1 (en) 2004-03-12 2008-04-17 Biodel, Inc. Rapid Acting Injectable Insulin Compositions
US8673360B2 (en) 2004-08-10 2014-03-18 Shin Nippon Biomedical Laboratories, Ltd. Compositions that enable rapid-acting and highly absorptive intranasal administration
ATE486064T1 (de) 2004-08-20 2010-11-15 Mannkind Corp Katalyse der diketopiperazinsynthese
PL1791542T3 (pl) 2004-08-23 2015-11-30 Mannkind Corp Sole diketopiperazyny do dostarczania leków
US7115561B2 (en) * 2004-09-22 2006-10-03 Patterson James A Medicament composition and method of administration
GB2420707A (en) * 2004-10-11 2006-06-07 Nasaleze Patents Ltd Compositions for intranasal administration
AU2006290870B2 (en) 2005-09-14 2013-02-28 Mannkind Corporation Method of drug formulation based on increasing the affinity of active agents for crystalline microparticle surfaces
EP2497484A3 (en) 2006-02-22 2012-11-07 MannKind Corporation A method for improving the pharmaceutic properties of microparticles comprising diketopiperazine and an active agent
JP5415769B2 (ja) * 2006-12-26 2014-02-12 株式会社新日本科学 経鼻投与用製剤
US8485180B2 (en) 2008-06-13 2013-07-16 Mannkind Corporation Dry powder drug delivery system
DK2570147T3 (da) 2008-06-13 2018-01-29 Mannkind Corp Tørpulverinhalator og system til lægemiddelindgivelse
KR101628410B1 (ko) 2008-06-20 2016-06-08 맨카인드 코포레이션 흡입 활동에 관한 실시간 프로파일링을 위한 대화형 장치 및 방법
TWI532497B (zh) 2008-08-11 2016-05-11 曼凱公司 超快起作用胰島素之用途
US8314106B2 (en) 2008-12-29 2012-11-20 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
CA2754595C (en) 2009-03-11 2017-06-27 Mannkind Corporation Apparatus, system and method for measuring resistance of an inhaler
WO2010131486A1 (en) 2009-05-15 2010-11-18 Shin Nippon Biomedical Laboratories, Ltd. Intranasal pharmaceutical compositions with improved pharmacokinetics
US8734845B2 (en) 2009-06-12 2014-05-27 Mannkind Corporation Diketopiperazine microparticles with defined specific surface areas
WO2011013003A2 (en) 2009-07-31 2011-02-03 Shin Nippon Biomedical Laboratories, Ltd. Intranasal granisetron and nasal applicator
CA2778698A1 (en) 2009-11-03 2011-05-12 Mannkind Corporation An apparatus and method for simulating inhalation efforts
RU2531455C2 (ru) 2010-06-21 2014-10-20 Маннкайнд Корпорейшн Системы и способы доставки сухих порошковых лекарств
MX350838B (es) 2011-02-11 2017-09-18 Grain Proc Corporation * Composicion de sal.
MY180552A (en) 2011-04-01 2020-12-02 Mannkind Corp Blister package for pharmaceutical cartridges
WO2012174472A1 (en) 2011-06-17 2012-12-20 Mannkind Corporation High capacity diketopiperazine microparticles
WO2013063160A1 (en) 2011-10-24 2013-05-02 Mannkind Corporation Methods and compositions for treating pain
US9789071B2 (en) 2012-06-27 2017-10-17 G2B Pharma, Inc. Intranasal formulation of epinephrine for the treatment of anaphylaxis
CA2878457C (en) 2012-07-12 2021-01-19 Mannkind Corporation Dry powder drug delivery systems and methods
WO2014066856A1 (en) 2012-10-26 2014-05-01 Mannkind Corporation Inhalable influenza vaccine compositions and methods
RU2715714C2 (ru) 2013-03-04 2020-03-03 Безен Хелткэа Люксембург Сарл Сухие фармацевтические композиции, включающие наночастицы активного агента, связанные с частицами носителя
BR112015023168B1 (pt) 2013-03-15 2021-08-10 Mannkind Corporation Composição de 3,6-bis(n-fumaril-4-aminobutil)-2,5-dicetopiperazina cristalina, método de produção de partículas de 3,6-bis(n-fumaril-4-aminobutil)-2,5-dicetopiperazina e uso de uma composição de dicetopiperazina cristalina
CN114848614A (zh) 2013-07-18 2022-08-05 曼金德公司 热稳定性干粉药物组合物和方法
CA2920488C (en) 2013-08-05 2022-04-26 Mannkind Corporation Insufflation apparatus and methods
AU2014315459A1 (en) * 2013-09-03 2016-04-07 G2B Pharma Inc. Intranasal formulation for the treatment of cardiopulmonary resuscitation (CPR), cardiac life support (CLS), anaphylaxis and/or anaphylactoid reactions
ES2904570T3 (es) * 2013-09-24 2022-04-05 Satsuma Pharmaceuticals Inc Formulación de DHE intranasal para el tratamiento del dolor de cabeza
US10307464B2 (en) 2014-03-28 2019-06-04 Mannkind Corporation Use of ultrarapid acting insulin
US10561806B2 (en) 2014-10-02 2020-02-18 Mannkind Corporation Mouthpiece cover for an inhaler
KR20180023884A (ko) 2015-01-07 2018-03-07 트라이제미나 인코퍼레이티드 마그네슘-함유 옥시토신 제제 및 사용 방법
US11744967B2 (en) 2017-09-26 2023-09-05 Shin Nippon Biomedical Laboratories, Ltd. Intranasal delivery devices
EP3893877A4 (en) 2018-12-11 2022-09-14 Satsuma Pharmaceuticals, Inc. COMPOSITIONS, DEVICES AND METHODS FOR TREATMENT OR PREVENTION OF HEADACHE
EP4232006A4 (en) * 2020-12-16 2024-05-08 Liw Innovation Ab NEW POWDER COMPOSITION
WO2023192691A2 (en) * 2022-04-01 2023-10-05 Wake Forest University Health Sciences Methods and formulations for intranasal delivery of insulin in the treatment of diabetic eye disease

Family Cites Families (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2445300A (en) * 1941-12-05 1948-07-13 Univ Pennsylvania Virus vaccines
US2445301A (en) * 1941-12-05 1948-07-13 Univ Pennsylvania Influenza vaccine
GB668341A (en) * 1948-11-18 1952-03-12 Armour & Co Improvements in powder dispensers
BE509861A (ko) * 1952-03-13
US2798835A (en) * 1954-01-18 1957-07-09 American Cyanamid Co Newcastle disease and infectious bronchitis vaccines and production thereof
US2959325A (en) * 1954-04-29 1960-11-08 Risdon Mfg Co Method and apparatus for dispensing dry powders
US2908614A (en) * 1954-08-10 1959-10-13 Glaxo Lab Ltd Use of dextran in freeze-drying process
BE556587A (ko) * 1957-01-31 1957-04-11
US2946724A (en) * 1957-05-29 1960-07-26 American Cyanamid Co Stable poliomyelitis live virus vaccine
US3155573A (en) * 1958-05-06 1964-11-03 Benger Lab Ltd Inhalant composition and method of making same
US3186908A (en) * 1962-08-16 1965-06-01 Parke Davis & Co Calcium lactobionate stabilization of labile antigenic virus vaccine materials
FR2530M (fr) * 1962-10-01 1964-06-19 Leon Georges Chevance Médicament antivirus respiratoire.
BE629985A (ko) * 1962-11-29
FR1538322A (fr) * 1966-11-21 1968-09-06 Rhone Poulenc Sa Procédé de préparation d'une suspension virale inactivée
GB1230472A (ko) * 1967-07-10 1971-05-05
US3957965A (en) * 1967-08-08 1976-05-18 Fisons Limited Sodium chromoglycate inhalation medicament
GB1242211A (en) * 1967-08-08 1971-08-11 Fisons Pharmaceuticals Ltd Pharmaceutical composition
GB1163470A (en) * 1967-11-13 1969-09-04 Cecil Arthur Clark Improvements in or relating to Adjuvant Vaccines
FR7461M (ko) * 1968-06-19 1970-01-05
US3544680A (en) * 1968-10-09 1970-12-01 Wistar Inst Intranasal immunization against rubella
FR8202M (ko) * 1968-10-31 1970-09-14
NL7012832A (ko) * 1970-08-29 1972-03-02
GB1381872A (en) * 1971-06-22 1975-01-29 Fisons Ltd Pharmaceutical compositions for inhalation
DE2254043C2 (de) * 1972-11-04 1985-01-24 Hoechst Ag, 6230 Frankfurt LH-Releasing Hormon zur nasalen Applikation
DE2254061A1 (de) * 1972-11-04 1974-05-16 Hoechst Ag Lh-releasing hormon zur nasalen applikation
US3915794A (en) * 1973-02-09 1975-10-28 Rit Rech Ind Therapeut Stabilizing compositions for cell-free viruses and cell-free virus preparations containing them
US3953592A (en) * 1973-09-27 1976-04-27 Recherche Et Industrie Therapeutiques (R.I.T.) Live influenza virus vaccines and preparation thereof
FR2262962B1 (ko) * 1974-03-05 1977-11-04 Science Union & Cie
DE2535258C2 (de) * 1974-08-10 1993-06-03 Fisons Plc, Ipswich, Suffolk Inhalierbares Medikament in Pelletform
DK143689C (da) * 1975-03-20 1982-03-15 J Kreuter Fremgangsmaade til fremstilling af en adsorberet vaccine
GB1521000A (en) * 1975-06-13 1978-08-09 Syntex Puerto Rico Inc Inhalation device
GB1527605A (en) * 1975-08-20 1978-10-04 Takeda Chemical Industries Ltd Insulin preparation for intranasal administration
US4147772A (en) * 1976-02-03 1979-04-03 Merck & Co., Inc. Vaccine stabilizer
GB1561835A (en) * 1976-02-11 1980-03-05 Allen & Hanburys Ltd Devices for dispensing medicamtens
US4053583A (en) * 1976-03-01 1977-10-11 Smithkline Corporation Live newcastle disease virus vaccines
US4110427A (en) * 1976-04-14 1978-08-29 The Risdon Manufacturing Company Powdered solid aerosol composition and method of manufacture
FR2352556A1 (fr) * 1976-05-26 1977-12-23 Pasteur Institut Inhalateur de poudre
DE2726837A1 (de) * 1976-06-18 1977-12-29 Rit Rech Ind Therapeut Impfstoff aus attenuiertem influenzavirus, verfahren zu seiner herstellung und seine verwendung bei der bekaempfung der influenza
BE853923A (fr) * 1977-04-25 1977-10-25 Rit Rech Ind Therapeut Nouveau vaccin vivant ameliore contre le pseudopeste aviaire et son procede de preparation
GB1591405A (en) * 1977-04-29 1981-06-24 Allen & Hanburys Ltd Device for dispensing medicaments
GB1571629A (en) * 1977-11-30 1980-07-16 Fisons Ltd Pharmaceutical compositions containing beclomethasone dipropionate
NL7811486A (nl) * 1977-11-30 1979-06-01 Fisons Ltd Nieuwe dipyranderivaten.
GB2016015B (en) * 1978-01-22 1982-05-06 Hayashibara Co Method of preparing interferon and preparations containing interferon
EP0007895B1 (fr) * 1978-07-19 1983-06-22 Patrick Couvreur Nanoparticules biodégradables, compositions pharmaceutiques les contenant et procédé pour leur préparation
JPS5529524A (en) * 1978-08-21 1980-03-01 Toyo Aerosol Kogyo Kk Powdery aerosol composition
ATE212T1 (de) * 1978-12-07 1981-10-15 Iowa State University Research Foundation, Inc., Intrarespiratorischer impfstoff, darin verwendeter modifizierter bakteriumstamm, dosierungsform des impfstoffes und verfahren zu seiner herstellung.
GB2042888B (en) * 1979-03-05 1983-09-28 Teijin Ltd Preparation for administration to the mucosa of the oral or nasal cavity
JPS6034925B2 (ja) * 1979-07-31 1985-08-12 帝人株式会社 持続性鼻腔用製剤およびその製造法
US4251509A (en) * 1980-01-31 1981-02-17 Wisconsin Alumni Research Foundation Dry particulate vaccine for oral administration
US4512972A (en) * 1980-06-30 1985-04-23 Kureha Chemical Industry Co., Ltd. Nasal preparation and processes for their production
JPS607965B2 (ja) * 1980-08-07 1985-02-28 帝人株式会社 鼻腔粘膜投与用粉剤の製造法
EP0094157B1 (en) * 1982-04-30 1987-07-29 Takeda Chemical Industries, Ltd. Pharmaceutical composition and its use

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6797258B2 (en) 1992-07-08 2004-09-28 Nektar Therapeutics Compositions and methods for the pulmonary delivery of aerosolized macromolecules
US6737045B2 (en) 1994-03-07 2004-05-18 Nektar Therapeutics Methods and compositions for the pulmonary delivery insulin
US7744925B2 (en) 1994-12-02 2010-06-29 Quadrant Drug Delivery Limited Solid dose delivery vehicle and methods of making same
US7780991B2 (en) 1994-12-02 2010-08-24 Quadrant Drug Delivery Limited Solid dose delivery vehicle and methods of making same
US7785631B2 (en) 1994-12-02 2010-08-31 Quadrant Drug Delivery Limited Solid dose delivery vehicle and methods of making same
US8802149B2 (en) 1996-12-31 2014-08-12 Novartis Pharma Ag Systems and processes for spray drying hydrophobic and hydrophilic components
US8337895B2 (en) 2000-06-30 2012-12-25 Novartis Ag Spray drying process control of drying kinetics
WO2003004048A1 (en) * 2001-07-05 2003-01-16 Translational Research Ltd. Compositions for nasal administration of insulin
US8084420B2 (en) 2005-09-29 2011-12-27 Biodel Inc. Rapid acting and long acting insulin combination formulations
US7713929B2 (en) 2006-04-12 2010-05-11 Biodel Inc. Rapid acting and long acting insulin combination formulations
US9060927B2 (en) 2009-03-03 2015-06-23 Biodel Inc. Insulin formulations for rapid uptake

Also Published As

Publication number Publication date
EP0122036A1 (en) 1984-10-17
US4613500A (en) 1986-09-23
JPS6237016B2 (ko) 1987-08-10
DE3476633D1 (en) 1989-03-16
EP0122036B1 (en) 1989-02-08
JPS59163313A (ja) 1984-09-14

Similar Documents

Publication Publication Date Title
EP0122036B2 (en) Powdery pharmaceutical composition for nasal administration
US4985242A (en) Intranasally applicable powdery pharmaceutical composition
EP0943326B2 (en) Powdery composition for nasal administration
US5011678A (en) Composition and method for administration of pharmaceutically active substances
KR100611025B1 (ko) 분말상 경비 조성물
US4788221A (en) Pharmaceutical compositions comprising calcitonin and an absorption-promoting substance
NO178564B (no) Framgangsmåte for framstilling av et system for administrering av aktive medikamenter gjennom slimhinner
JPS6242888B2 (ko)
EP1108423B1 (en) Powdery pernasal compositions
CA2375914A1 (en) Formulations comprising dehydrated particles of pharmaceutical agents and process for preparing the same
JP3197221B2 (ja) 吸収性が改善された粉末状経鼻投与組成物
GB2193891A (en) Nasal pharmaceutical compositions containing octreotide
JP2505430B2 (ja) 塩基性アミノ酸を含有する経鼻投与用粉末状組成物
JPH08277226A (ja) 経鼻吸収用生理活性ペプチド組成物
JP3197223B2 (ja) 即効性と持続性を兼ね備えた粉末状経鼻投与用組成物
JPH06172199A (ja) ペプチド類経鼻投与用組成物
Chang et al. Nasal drug delivery
JPH0480008B2 (ko)
JP3197222B2 (ja) 粉末状経鼻投与組成物
JPS6339822A (ja) カルシトニン経鼻剤
JPS63115820A (ja) アスコルビン酸類を含有する経鼻投与用粉末状組成物
JP2002128704A (ja) 経鼻投与用組成物
IE60761B1 (en) Novel galenical formulations
CN106924723A (zh) 经口腔黏膜给药的含人胰高血糖素样肽‑1类似物的药物组合物
JPH0524129B2 (ko)

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Designated state(s): CH DE FR GB IT LI SE

17P Request for examination filed

Effective date: 19850102

17Q First examination report despatched

Effective date: 19860625

R17C First examination report despatched (corrected)

Effective date: 19870615

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): CH DE FR GB IT LI SE

REF Corresponds to:

Ref document number: 3476633

Country of ref document: DE

Date of ref document: 19890316

ITF It: translation for a ep patent filed

Owner name: STUDIO TORTA SOCIETA' SEMPLICE

ET Fr: translation filed
PLBI Opposition filed

Free format text: ORIGINAL CODE: 0009260

26 Opposition filed

Opponent name: NOVO-NORDISK A/S

Effective date: 19891108

Opponent name: FARMITALIA CARLO ERBA S.R.L.

Effective date: 19891108

Opponent name: PHARMACIA AB

Effective date: 19891107

Opponent name: DANBIOSYST UK LTD

Effective date: 19891106

ITTA It: last paid annual fee
PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

R26 Opposition filed (corrected)

Opponent name: DANBIOSYST UK LTD * 891107 PHARMACIA BIOSYSTEMS A

Effective date: 19891106

PUAH Patent maintained in amended form

Free format text: ORIGINAL CODE: 0009272

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: PATENT MAINTAINED AS AMENDED

27A Patent maintained in amended form

Effective date: 19941102

AK Designated contracting states

Kind code of ref document: B2

Designated state(s): CH DE FR GB IT LI SE

REG Reference to a national code

Ref country code: CH

Ref legal event code: AEN

ET3 Fr: translation filed ** decision concerning opposition
ITF It: translation for a ep patent filed

Owner name: STUDIO TORTA SOCIETA' SEMPLICE

EAL Se: european patent in force in sweden

Ref document number: 84301546.2

APAC Appeal dossier modified

Free format text: ORIGINAL CODE: EPIDOS NOAPO

APAC Appeal dossier modified

Free format text: ORIGINAL CODE: EPIDOS NOAPO

REG Reference to a national code

Ref country code: GB

Ref legal event code: IF02

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 20021224

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 20021227

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20030224

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20030225

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20030310

Year of fee payment: 20

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20040307

Ref country code: GB

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20040307

Ref country code: CH

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20040307

REG Reference to a national code

Ref country code: GB

Ref legal event code: PE20

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

EUG Se: european patent has lapsed
APAH Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOSCREFNO

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO